Journal of Food and Nutrition Research
ISSN (Print): 2333-1119 ISSN (Online): 2333-1240 Website: Editor-in-chief: Prabhat Kumar Mandal
Open Access
Journal Browser
Journal of Food and Nutrition Research. 2019, 7(12), 821-826
DOI: 10.12691/jfnr-7-12-2
Open AccessArticle

Effects of Fish Meat-derived Peptide and Dipeptides on Dexamethasone-induced Fatigue in Mice

Yusuke Iwasaki1, Hiroyasu Sakai2, Maho Asami2, Satoko Kitora2, Hiroaki Naito2, Risako Kon2, Nobutomo Ikarashi2 and Junzo Kamei1, 2,

1Department of Biopharmaceutics and Analytical Science, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-5501, Japan

2Department of Biomolecular Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-5501, Japan

Pub. Date: December 12, 2019

Cite this paper:
Yusuke Iwasaki, Hiroyasu Sakai, Maho Asami, Satoko Kitora, Hiroaki Naito, Risako Kon, Nobutomo Ikarashi and Junzo Kamei. Effects of Fish Meat-derived Peptide and Dipeptides on Dexamethasone-induced Fatigue in Mice. Journal of Food and Nutrition Research. 2019; 7(12):821-826. doi: 10.12691/jfnr-7-12-2


In patients with inflammatory diseases, exogenous glucocorticoids have become the most common cause of drug-induced muscle wasting. In this study, we showed that isoleucine-arginine (IR) and arginine-isoleucine (RI) are the main dipeptides with antioxidant activity in fish meat-derived peptide extract (FMDP). To investigate the anti-fatigue effect of FMDP and the two dipeptides (IR or RI), dexamethasone (DEX)-treated mice performed a weighted forced swimming test. Despite no change in body weight, the shortened swim time after DEX administration returned to baseline levels following the administration of FMDP, IR, and RI. However, the swim time of naive mice cannot be extended with the administration of FMDP, IR, or RI. Our data suggest that FMDP, IR, and RI may have beneficial effects on DEX-induced fatigue in mice. Nevertheless, further research is required to determine the mechanism through which FMDP reduces fatigue.

antioxidant activity fish meat-derived peptide dexamethasone fatigue electron spin resonance

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit


Figure of 5


[1]  World Health Organization. “World health statistics 2018: monitoring health for the SDGs”, 2018.
[2]  D'Autreaux, B. and Toledano, M.B. “ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis”, Nat Rev Mol Cell Biol, 8, 813-824, 2007.
[3]  Gao, X., Wilsgaard, T., Jansen, E., Xuan, Y., Anusruti, A., Brenner, H. and Schottker, B. “Serum total thiol levels and the risk of lung, colorectal, breast and prostate cancer: A prospective case-cohort study”, Int J Cancer, 2019.
[4]  Mathis, K.W., Venegas-Pont, M., Masterson, C.W., Stewart, N.J., Wasson, K.L. and Ryan, M.J. “Oxidative stress promotes hypertension and albuminuria during the autoimmune disease systemic lupus erythematosus”, Hypertension, 59, 673-679, 2012.
[5]  Papada, E., Forbes, A., Amerikanou, C., Torovic, L., Kalogeropoulos, N., Tzavara, C., Triantafillidis, J.K. and Kaliora, A.C. “Antioxidative efficacy of a Pistacia lentiscus supplement and its effect on the plasma amino acid profile in inflammatory bowel disease: A randomised, double-blind, placebo-controlled trial”, Nutrients, 10, 2018.
[6]  Fukuda, S., Nojima, J., Motoki, Y., Yamaguti, K., Nakatomi, Y., Okawa, N., Fujiwara, K., Watanabe, Y. and Kuratsune, H. “A potential biomarker for fatigue: Oxidative stress and anti-oxidative activity”, Biol Psychol, 118, 88-93, 2016.
[7]  Ramamoorthy, S. and Cidlowski, J.A. “Exploring the molecular mechanisms of glucocorticoid receptor action from sensitivity to resistance”, Endocr Dev, 24, 41-56, 2013.
[8]  Dardevet, D., Sornet, C., Taillandier, D., Savary, I., Attaix, D. and Grizard, J. “Sensitivity and protein turnover response to glucocorticoids are different in skeletal muscle from adult and old rats. Lack of regulation of the ubiquitin-proteasome proteolytic pathway in aging”, J Clin Invest, 96, 2113-2119, 1995.
[9]  Mitch, W.E. and Goldberg, A.L. “Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway”, N Engl J Med, 335, 1897-1905, 1996.
[10]  Gupta, A. and Gupta, Y. “Glucocorticoid-induced myopathy: Pathophysiology, diagnosis, and treatment”, Indian J Endocrinol Metab, 17, 913-916, 2013.
[11]  Huang, Y., Chen, K., Ren, Q., Yi, L., Zhu, J., Zhang, Q. and Mi, M. “Dihydromyricetin attenuates dexamethasone-induced muscle atrophy by improving mitochondrial function via the PGC-1alpha pathway”, Cell Physiol Biochem, 49, 758-779, 2018.
[12]  Begum, G., Cunliffe, A. and Leveritt, M. “Physiological role of carnosine in contracting muscle”, Int J Sport Nutr Exerc Metab, 15, 493-514, 2005.
[13]  Schindler, A., Dunkel, A., Stahler, F., Backes, M., Ley, J., Meyerhof, W. and Hofmann, T. “Discovery of salt taste enhancing arginyl dipeptides in protein digests and fermented fish sauces by means of a sensomics approach”, J Agric Food Chem, 59, 12578-12588, 2011.
[14]  Ohba, T., Domoto, S., Tanaka, M., Nakamura, S., Shimazawa, M. and Hara, H. “Myalgic encephalomyelitis/chronic fatigue syndrome induced by repeated forced swimming in mice”, Biol Pharm Bull, 42, 1140-1145, 2019.
[15]  Matsuoka, R., Kimura, M., Uno, S., Shidara, H. and Kunou, M. “Egg white hydrolysate improves fatigue due to short-term swimming load test in mice”, Food Sci Nutr, 6, 2314-2320, 2018.
[16]  Jiang, X., Chu, Q., Li, L., Qin, L., Hao, J., Kou, L., Lin, F. and Wang, D. “The anti-fatigue activities of Tuber melanosporum in a mouse model”, Exp Ther Med, 15, 3066-3073, 2018.
[17]  Schakman, O., Kalista, S., Barbe, C., Loumaye, A. and Thissen, J.P. “Glucocorticoid-induced skeletal muscle atrophy”, Int J Biochem Cell Biol, 45, 2163-2172, 2013.
[18]  Gordon, B.S., Kelleher, A.R. and Kimball, S.R. “Regulation of muscle protein synthesis and the effects of catabolic states”, Int J Biochem Cell Biol, 45, 2147-2157, 2013.
[19]  Bentzinger, C.F., Romanino, K., Cloetta, D., Lin, S., Mascarenhas, J.B., Oliveri, F., Xia, J., Casanova, E., Costa, C.F., Brink, M., Zorzato, F., Hall, M.N. and Ruegg, M.A. “Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy”, Cell Metab, 8, 411-424, 2008.
[20]  Brugarolas, J., Lei, K., Hurley, R.L., Manning, B.D., Reiling, J.H., Hafen, E., Witters, L.A., Ellisen, L.W. and Kaelin, W.G., Jr. “Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex”, Genes Dev, 18, 2893-2904, 2004.
[21]  Katiyar, S., Liu, E., Knutzen, C.A., Lang, E.S., Lombardo, C.R., Sankar, S., Toth, J.I., Petroski, M.D., Ronai, Z. and Chiang, G.G. “REDD1, an inhibitor of mTOR signalling, is regulated by the CUL4A-DDB1 ubiquitin ligase”, EMBO Rep, 10, 866-872, 2009.
[22]  Ellisen, L.W., Ramsayer, K.D., Johannessen, C.M., Yang, A., Beppu, H., Minda, K., Oliner, J.D., McKeon, F. and Haber, D.A. “REDD1, a developmentally regulated transcriptional target of p63 and p53, links p63 to regulation of reactive oxygen species”, Mol Cell, 10, 995-1005, 2002.
[23]  Lin, L., Stringfield, T.M., Shi, X. and Chen, Y. “Arsenite induces a cell stress-response gene, RTP801, through reactive oxygen species and transcription factors Elk-1 and CCAAT/enhancer-binding protein”, Biochem J, 392, 93-102, 2005.
[24]  Braun, T.P. and Marks, D.L. “The regulation of muscle mass by endogenous glucocorticoids”, Front Physiol, 6, 12, 2015.
[25]  McClung, J.M., Judge, A.R., Powers, S.K. and Yan, Z. “p38 MAPK links oxidative stress to autophagy-related gene expression in cachectic muscle wasting”, Am J Physiol Cell Physiol, 298, C542-549, 2010.